CN87104429A - 用于药剂的控制性释放基体 - Google Patents
用于药剂的控制性释放基体 Download PDFInfo
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- CN87104429A CN87104429A CN87104429.3A CN87104429A CN87104429A CN 87104429 A CN87104429 A CN 87104429A CN 87104429 A CN87104429 A CN 87104429A CN 87104429 A CN87104429 A CN 87104429A
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Classifications
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Abstract
采用高级脂族醇和丙烯酸树脂的组合物作为基体材料,可延长起治疗作用的活性剂从控制性释放基体中的释放时间。
Description
在药学技术领域中,人们业已知道制备某些经人和动物口服后能缓慢地释放其内所含的药理学活性物质的药剂。这类缓慢释放的药剂系用于延缓药物在到达消化道某些部位前的吸收。而药物在消化道内的此种控制性释放则可进一步使所说药物在血液中维持所需浓度的持续时间较之服用普通快速释放药剂的长。
在该技术领域中缓慢地释放的配方特别包括有包衣的药丸和药片,以及胶囊(剂),其中活性药物的缓慢释放是通过局部拆开制剂上的包衣,或使其与特别的基体结合,以影响药物的释放而实现。某些缓慢释放的配方提供了一次剂量活性化合物在服用后预定时间内的相关连续释放。
所有缓慢释放的制剂的作用均在于使药物服用后的药理学反应时间较之通常服用快速释放药剂的长。这种较长的反应时间将为治疗带来许多内在的好处,是那些相应的作用时间短,即刻释放的制剂所不及的。由此,治疗可得以继续,而不必打断病人的睡眠,这在治疗下列病人时尤为重要:需防止夜间发作的癫痫病人,唤醒后会生偏头痛的病人,以及不间断睡眠是至关重要的衰弱病人。
长效(作用时间长)药物的另一重要作用体现在心血管系统疾病的治疗中,对此必须使血液中药物的最佳峰值浓度维持在稳定水平,以达到所需的疗效。除非普通快速作用药物的疗法是以频繁的间隔仔细地服用,以使血液中药物浓度保持在有效的稳定水平,否则由于快速吸收、该化合物的全身排泄、以及通过新陈代谢失效,血液中活性药物的浓度将出现峰值和谷值,因而在病人疗程中将产生一些额外问题。长效药剂的另一共同优点是减少病人为避免因疏忽而漏服药物所引起的依从性。
已有技术所给出的那些能使活性化合物从载体中缓慢地释放的药剂的制备和应用基本上与活性物质释放到消化道的生理液中有关。然而,人们普通认为,若仅有活性物质存在于胃肠液中,则它不能单独地确保生物药效率。在更富有意义的含义上,生物药效率是指服用单位剂量药剂后,人体对药物的吸收达到对靶组织部位有效的程度或量。
活性药物必须处于溶解状态才能被人体吸收。单位剂量药剂内所含的一定量的活性药物溶于合适生理液中所需的时间称为溶化时间。从单位剂量药剂中活性物质的溶化时间系由标准条件下所进行的试验方法而测得的该单位剂量药剂在规定时间内所释放的活性药物量的比例来确定。胃肠道的生理液是确定溶化时间的介质。目前技术发展水平提供了许多用以测定药剂溶化时间的令人满意的试验方法,这些试验方法在世界范围的正式摘要性文件均有描述。
虽然影响药物从其载体中溶解出来的因素很多,但对于某一特定药剂中的药理学活性物质所测得的溶化时间却是相对恒定,并可重现。影响溶化时间的各种因素包括暴露在溶剂介质中的药物表面积,溶液PH值,在具体溶剂中物质的溶解度,以及溶剂中溶质饱和浓度的推动力。因此,当组分被组织的某一部位吸收而从溶解介质中除去后,则活性药物的溶解浓度在其平衡状态下呈动态变化。在生理学条件下,溶解物质的饱和量从药剂的储备量中得到补充,使溶剂中保持较为均匀和恒定的溶解物浓度,以进行稳态吸收。
鉴于(胃肠道)膜两边活性物质浓度之差,亦即活性物质在胃肠液中溶解量与血液中存在量之差为推动力的方向,因而穿过胃肠道组织吸收部位的输运受到膜两边道南渗透平衡力影响。由于血液浓度受到稀释、循环变化、组织贮备、新陈代谢转化和全身排泄的影响而不断降低,因此活性物质是从胃肠道流向血液。
尽管有多种因素影响药物的溶解和吸收,但对于某一药剂所测得的体外溶解时间和体内生物药效率之间的依从关系业已确定。这一关系在该技术领域中是如此牢固地确定,以至溶解时间一般已用来衡量某一单位剂量药剂中活性组分的潜在生物药效率。鉴于这一关系,显然在评价缓慢释放药剂时,对该药剂所测得的溶解时间是所考虑的重要基本特性之一。
如美国专利4,235,870所述,缓慢释放的药剂一般系用包含羟烷基纤维素组分和高级脂族醇的持续释放基体制备。虽然这类具有持续释放基体的药剂在该技术领域内已具有一定的进步性,但人们仍在谋求对其进行改进,特别当活性药物具有较高水溶性时更是如此。
因此,本发明的主要目的是提供一种新颖的持续释放基体,它能延长与其相结合的活性药物的释放时间。
本发明的另一目的是提供一种供药剂用的新颖持续释放基体,它能延长活性药物的释放时间,这在活性药物具有较高水溶性时特别有效。
本发明的又一目的是提供一种含有持续释放基体的药剂,它适用于各种类型的药学活性组分,并能延长所有这些组分的释放时间。
本发明的其他目的和优点可从进一步阅读说明书及所附的权利要求书而清楚地体现出来。
鉴于上述及其他目的,本发明主要包括那些能在预定或规定的一段时间内有控制地缓慢释放起治疗作用之活性组分的药剂,而所说药剂包含作为基体成分的高级脂族醇与丙烯酸树脂的组合物。由这类高级脂族醇和丙烯酸树脂作为基体而制备的药剂经人或动物施用(一般为口服)后,可在5小时,甚至多达24小时的时间内持续地释放起治疗作用的活性组分。
本发明的基体系由任何药学上可接受的高级脂族醇制备,最好是含有10至18个碳原子的脂族醇,其中尤以十八烷醇、十六烷醇、十八醇十六醇混合物、十二烷醇、十四烷醇、以及它们的混合物为佳。
对于本发明来说,任何药学上可接受的丙烯酸聚合物均可使用。所说丙烯酸聚合物可以是阳离子、阴离子或非离子型物质,如丙烯酸盐、由异丁烯酸形成的异丁烯酸盐或异丁烯酸脂。这些聚合物可由人工合成如上所述的阳离子、阴离子或非离子型物质,所得聚合物对PH有一定依赖关系,因而,可在较宽的PH范围内溶或不溶于溶液中。就本发明而言,最有效的丙烯酸聚合物是西德Weiterstat的Rohm Pharma.GmbH公司出品,销售商品名称为“EUDRAGIT”的丙烯酸聚合物。
从本发明的基体制备片剂之类药品时,可以使用其他赋形剂,这类赋形剂一般是用于制片或胶囊充填工艺中所用的惰性辅助物质,例如可包括聚乙烯吡咯烷酮之类的粘结剂、乳糖类填充剂、玉米淀粉类崩解剂、以及硬脂酸镁之类的润滑剂。
在制备本发明的基体时,用至少一步湿法(水或有机溶剂)制粒工艺将两种基本物料,即高级脂族醇和丙烯酸树脂结合在一起,以形成一种连同制粒或胶囊充填所需的任何其他赋形剂在内的均匀颗粒。在制粒过程中可使一种或一种以上的治疗剂与其他物料相结合,或使之与制备后的颗粒混合。
一般采用“湿”式制粒法制备颗粒,亦即在有(或没有)一种或一种以上治疗剂存在的情况下,将大部分赋形剂与成粒液相混合,直至得到湿的粒状物。然后使其干燥至仅在颗粒中保留以残留水分形式存在的微量流体。接着再用合适的筛分设备对颗粒进行筛分,由此得到其后能充填在胶囊中,或被压制成片剂或小丸状(Caplet)的可流动粉末。意外地发现,高级脂族醇与丙烯酸聚合物的组合对于延缓起治疗作用的活性组分的释放有协同作用。这一现象对于高水溶性的活性物质特别有利。
业已注意到,若想对普通控制性释放片剂中某些高水溶性的药理学活性组分(如羟氢可待酮)的释放进行控制,则难于达到延缓或逐渐释放的目的。然而,在将诸如羟氢可待酮之类的高水溶性药理学活性物质结合到本发明的基体体系中时,则可清楚地观察到所说活性物质的控制性释放现象。用于测试控制性释放的方法系上述美国专利XXⅠ节中所述的溶解技术。
按照本发明,用作控制性释放基体的高级脂族醇和丙烯酸树脂所形成的组合物中,丙烯酸树脂的量宜在10%-60%之间(以丙烯酸树脂和脂族醇的总量为基准),最好为15%-40%,而其中尤以约20%-35%为更佳。以上百分数均以重量计。
业已发现,若将丙烯酸树脂与高级脂族醇一起使用时,则将对药物流动和控制性释放的药物释放性能的控制产生一种意想不到的强化作用,其中较佳丙烯酸树脂是销售商标为Eudragit一类的商品,尤以Eudragit RL,RS,S,E30D和L30为更佳。上述强化作用在使用高水溶性治疗剂时特别明显。
采用脂族醇和丙烯酸树脂的组合物作为治疗剂的基体将产生最佳的药物释放控制,延缓时间一般为5-12小时,最长可达24小时,其中本发明之基体用量若以选用的配料部分的总重量计,则在20%-40%的范围内。基体量为下限的药剂,释放时间一般为5小时,而随着控制释放基体重量百分数的增加,延缓药物释放的时间也随之增加。
以下给出的实施例将对本发明作进一步说明,然而,本发明的范围并不意味着限于这些实施例的具体细节。
实施例1
将支气管扩张药-氨茶碱(即茶碱的1,2-乙二胺盐)在本发明的缓慢释放体系中进行试验。
欲制备一种活性组分含量为225毫克的控制性释放的氨茶碱药片。
下列三种片剂验证了本发明的原理,以及对于药学用途的适用性和优点。
配方A 配方B 配方C
成分 mg mg mg
氨茶碱 225.0 225.0 115.0
聚乙烯基吡咯烷酮 3.4 3.4 3.4
Eudragit RS / 10.0 20.0
丙酮/异丙醇 适量 适量 适量
十八醇十六醇混合物 86.6 76.6 66.6
硬脂酸镁 2.4 2.4 2.4
滑石 6.0 6.0 6.0
合计 323.4 323.4 323.4
上述片剂系按照下述方法制备:
将氨茶碱和聚乙烯基吡咯烷酮放在合适的混合装置中均匀地拌和,同时将e udragit RS(在片剂B和C的情况下)溶于丙酮/异丙醇(50∶50)溶液中,以用作成粒液。然后将所得成粒液加到正在进行混合的粉末中,直至形成湿颗粒体,使之干燥后用12目筛子过筛。接着使所需量的十八醇十六醇混合物熔化(温度约60℃~70℃),并在合适的混合装置中,将其加到温热的颗粒体中。俟其冷却后,再用12目筛子对颗粒进行筛分。此后将润滑剂(滑石、硬脂酸镁)拌入颗粒中。
最后将上述制得的颗粒在装有直径为12/32英寸的圆形双凸面刀具之合适制片机中压制成片剂。
用上述美国专利中的浆式搅拌机(USP Paddle)以100转/分的转速条件下,先将制成的片剂在模拟胃液中暴露1小时,然后再暴露在模拟肠液中,溶解试验结果如下:
氨茶碱溶解率,%
小时
配方A 配方B 配方C
1 19.1 20.1 19.2
2 77.5 47.0 40.2
3 100.0 67.2 55.0
4 84.0 67.7
6 100.0 82.0
8 93.0
9 100.0
从以上溶解试验结果可以看出,当15%(10毫克/片)的十八醇十六醇混合物用丙烯酸树脂代替时,则100%氨茶碱的释放时间从3小时延长到6小时,而当丙烯酸树脂的替换百分数从15%增加到30%(20毫克/升)时,则100%氨茶碱的释放时间进一步延长到9小时。
实施例2
通过制备控制性释放的麻醉性镇痛药片-羟氢可待酮来进一步验证本发明的效用。
欲制备一种能在大约9至10小时的时间内,有控制地渐渐释放出活性物质的羟氢可待酮控制性释放片剂。所说片剂配方如下:
成分 配方A,mg/片 配方B,mg/片
羟氢可待酮 9.2 9.2
乳糖 200.0 200.0
Eudragit E30D(固体) / 11.2
水 适量 /
十八烷醇 61.2 50.0
硬酯酸 5.3 5.3
滑石 5.3 5.3
合计 281.0 281.0
上述片剂制备方法如下:将羟氢可待酮和乳糖放在合适的混合装置中均匀地拌和,然后将成粒液加到混合粉末中,使之成细粒状。在片剂A的情况下,成粒液是水,而片剂B的成粒液为丙烯酸悬浮液“Eudragit E30D”,即浓度为30%的丙烯酸树脂水悬浮液,其用量相当于每片片剂含有11.2毫克固体树脂物质。颗粒经干燥后,再通过12目筛子过筛。然后使用合适的混合器,将熔化后的十八烷醇加到温热的细粒中。俟其冷却,再用12目筛子过筛。接着将通过筛子的颗粒与滑石粉和硬脂酸混合,而予以润滑。最后在装有直径为10/32英寸的圆形双凸面刀具的合适制片机中压制成片剂。
用上述美国专利中的浆式搅拌机以100转/分的转速条件下,先将制成的片剂在模拟胃液中暴露1小时,然后再暴露在模拟肠液中,溶解试验结果如下:
小时 羟氢可待酮溶解率,%
片剂A 片剂B
1 43.0 16.0
2 83.0 51.0
3 91.0 64.0
4 97.0 70.0
5 100.0 76.0
6 78.0
8 96.0
9 100.0
通过将上表中片剂A与片剂B的溶解试验结果进行比较,可以看出,当约为20%(11.2毫克/片)的十八烷醇用Eudragit E30D(作为最终配方中的固体物)替换时,则可更有效地控制片剂配方中羟氢可待酮的释放,其100%的释放时间从5小时延长到9小时。
实施例3
欲制备一种β-类肾上腺素能阻滞药,也称“心得安”的缓慢释放制剂,使100%活性药物在9小时的时间内逐渐释放出来。为验证本发明的效用,特制定下列片剂配方(按上述例1中所述的制备方法):
成份 配方A,mg/片 配方B,mg/片
心得安 30.0 30.0
乳糖 91.5 91.5
Eudgrait S / 8.0
成粒液(丙酮/异丙醇 适量 适量
(IPA)/水)
十八醇十六醇混合物 24.0 16.0
滑石 3.0 3.0
硬酯酸镁 1.5 1.5
合计 150.0 150.0
用直径为9/32英寸的圆形双凸面刀具将上述配方的混合物压制成片剂。
片剂的溶解试验系在美国专利所述的滚筒(USP basket)中进行,转速为100转/分,而片剂先在模拟胃液中暴露1小时,然后再暴露在模拟肠液中,所得结果如下:
心得安溶解百分率,%
小时
配方A 配方B
1 46.4 36.4
2 70.4 55.8
3 84.5 67.7
4 94.4 78.3
5 100.0 84.3
6 / 90.4
8 / 96.0
9 / 100.0
因此,从表中可以看出,用丙烯酸树脂取代配方A中33%的十八醇十六醇混合物,可导致更有效地控制心得安的释放,使100%释放时间从5小时进一步延缓和延长至9小时。
实施例4
麻醉药吗啡对解痛非常有效,而在护理晚期癌症病人时,一种能在长时间内缓慢地释放吗啡的控制性释放片剂是极其合适的。下列两种片剂用以验证本发明之原理,以及将吗啡加到这类片剂中,而使活性药物在长达许多小时的时间内控制性地释放出来的适用性。
成分 配方A,mg/片 配方B,mg/片
硫酸吗啡 30.0 30.0
乳糖 79.5 79.5
Eudragit RL / 12.0
丙酮/异丙醇 适量 适量
十八烷醇 36.0 24.0
滑石 3.0 3.0
硬脂酸镁 1.5 1.5
150.0 150.0
上述配方的片剂系按照实施例1中所述的方法制备。
片剂的溶解试验(按照以上实施例中提到的美国专利所述的方法进行)结果如下:
吗啡溶解百分数,%
小时 配方A 配方B
1 31.8 35.7
2 48.9 49.3
3 62.6 55.9
4 72.5 61.4
6 84.3 66.5
8 100.0 72.2
12 82.8
18 100.0
由上表可以看出,若33%的十八醇十六醇混合物用丙烯酸树脂代替时,则可使100%药物释放的溶解时间从8小时延长至18小时。这种持久地释放吗啡的方式将因此可使这类片剂甚至适合一天服用一次。
上文已对高级脂族醇和丙烯酸树脂的各种配方,以及各种治疗剂均作了具体说明,显然,在不偏离本发明范围的前提下可对其进行各种改变和变换。这类变换均被包括在所附权利要求书的范围内。
Claims (16)
1、一种持续作用的控制性释放口服药剂的制备方法,所说药剂包括分散在控制性释放的芯子或基体中的药学活性剂,而所说芯子或基体包含具有10至18个碳原子的高级脂族醇和药学上可接受的丙烯酸树脂,其中所说丙烯酸树脂约占所说高级脂族醇和所说丙烯酸树脂总重量的10%~60%。
2、根据权利要求1所述的方法,其特征在于所说的丙烯酸树脂的含量约为15%~40%(以重量计)。
3、根据权利要求1所述的方法,其特征在于所说丙烯酸树脂的含量约为20~35%(以重量计)。
4、根据权利要求1所述的方法,其特征在于所说芯子或基体还包括粘结剂。
5、根据权利要求4所述的方法,其特征在于所说芯子或基体还包括填充剂。
6、根据权利要求5所述的方法,其特征在于所说芯子或基体还包括崩解剂。
7、根据权利要求6所述的方法,其特征在于所说芯子或基体还包括润滑剂。
8、根据权利要求1所述的方法,其特征在于所说芯子或基体约占所说药剂重量的20~40%。
9、根据权利要求1所述的方法,其特征在于所说药学活性剂是高水溶性物质。
10、根据权利要求1所述的方法,其特征在于所说药学活性剂是阿米替林、阿托品、氯苯吡胺、氯丙嗪、可待因、右旋溴苯吡胺、二苯基羟基胺、抗敏安、麻黄碱、莨菪碱、吗啡、羟氢可待酮、罂粟碱、苯丙醇胺、心得安、奎尼丁、东良菪醇、茶碱或甲硫哒嗪。
11、一种用于控制性释放口服药剂,并适合药学活性剂在其内分散的芯子或基体的制备方法,其特征在于所说芯子或基体包含具有10至18个碳原子的高级脂族醇和药学上可接受的丙烯酸树脂,而所说丙烯酸树脂约占所说高级脂族醇和所说丙烯酸树脂总重量的10%~60%。
12、根据权利要求11所述的方法,其特征在于所说丙烯酸树脂的含量约为15%~40%(以重量计)。
13、根据权利要求11所述的方法,其特征在于所说丙烯酸树脂的含量约为20%~35%。
14、根据权利要求1所述的方法,其特征在于所说药剂为片剂形式。
15、根据权利要求1所述的方法,其特征在于所说药剂为丸状(Caplet)形式。
16、根据权利要求1所述的方法,其特征在于所说药剂为胶囊形式。
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US887,340 | 1986-07-18 | ||
US06/887,340 US4861598A (en) | 1986-07-18 | 1986-07-18 | Controlled release bases for pharmaceuticals |
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Families Citing this family (141)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4970075A (en) * | 1986-07-18 | 1990-11-13 | Euroceltique, S.A. | Controlled release bases for pharmaceuticals |
US5266331A (en) † | 1991-11-27 | 1993-11-30 | Euroceltique, S.A. | Controlled release oxycodone compositions |
US5681585A (en) | 1991-12-24 | 1997-10-28 | Euro-Celtique, S.A. | Stabilized controlled release substrate having a coating derived from an aqueous dispersion of hydrophobic polymer |
US5958459A (en) * | 1991-12-24 | 1999-09-28 | Purdue Pharma L.P. | Opioid formulations having extended controlled released |
US5968551A (en) * | 1991-12-24 | 1999-10-19 | Purdue Pharma L.P. | Orally administrable opioid formulations having extended duration of effect |
US5478577A (en) * | 1993-11-23 | 1995-12-26 | Euroceltique, S.A. | Method of treating pain by administering 24 hour oral opioid formulations exhibiting rapid rate of initial rise of plasma drug level |
US20080075781A1 (en) * | 1992-11-25 | 2008-03-27 | Purdue Pharma Lp | Controlled release oxycodone compositions |
IL119660A (en) * | 1993-05-10 | 2002-09-12 | Euro Celtique Sa | Controlled release formulation comprising tramadol |
US20070275062A1 (en) * | 1993-06-18 | 2007-11-29 | Benjamin Oshlack | Controlled release oxycodone compositions |
IL109944A (en) * | 1993-07-01 | 1998-12-06 | Euro Celtique Sa | Continuous release dosage form containing morphine and a method of preparing such sustained release unit dosage forms |
IL110014A (en) * | 1993-07-01 | 1999-11-30 | Euro Celtique Sa | Solid controlled-release oral dosage forms of opioid analgesics |
US7740881B1 (en) | 1993-07-01 | 2010-06-22 | Purdue Pharma Lp | Method of treating humans with opioid formulations having extended controlled release |
US5879705A (en) * | 1993-07-27 | 1999-03-09 | Euro-Celtique S.A. | Sustained release compositions of morphine and a method of preparing pharmaceutical compositions |
EP1442745A1 (en) * | 1993-10-07 | 2004-08-04 | Euro-Celtique | Orally administrable opioid formulations having extended duration of effect |
KR100354702B1 (ko) * | 1993-11-23 | 2002-12-28 | 유로-셀티크 소시에떼 아노뉨 | 약학조성물의제조방법및서방형조성물 |
US5891471A (en) * | 1993-11-23 | 1999-04-06 | Euro-Celtique, S.A. | Pharmaceutical multiparticulates |
US5843480A (en) * | 1994-03-14 | 1998-12-01 | Euro-Celtique, S.A. | Controlled release diamorphine formulation |
US5430021A (en) * | 1994-03-18 | 1995-07-04 | Pharmavene, Inc. | Hydrophobic drug delivery systems |
US5484608A (en) * | 1994-03-28 | 1996-01-16 | Pharmavene, Inc. | Sustained-release drug delivery system |
ES2097087B1 (es) * | 1994-08-01 | 1997-12-16 | Univ Sevilla | Sistema de liberacion controlada de morfina y otros farmacos solubles en agua por complejacion con sustancias polimericas. |
GB9422154D0 (en) * | 1994-11-03 | 1994-12-21 | Euro Celtique Sa | Pharmaceutical compositions and method of producing the same |
US20020006438A1 (en) * | 1998-09-25 | 2002-01-17 | Benjamin Oshlack | Sustained release hydromorphone formulations exhibiting bimodal characteristics |
US5965161A (en) | 1994-11-04 | 1999-10-12 | Euro-Celtique, S.A. | Extruded multi-particulates |
GB9519363D0 (en) | 1995-09-22 | 1995-11-22 | Euro Celtique Sa | Pharmaceutical formulation |
US5811126A (en) * | 1995-10-02 | 1998-09-22 | Euro-Celtique, S.A. | Controlled release matrix for pharmaceuticals |
JPH1050306A (ja) * | 1996-07-31 | 1998-02-20 | Toyota Autom Loom Works Ltd | 水素吸蔵合金電極の製造方法 |
US6375957B1 (en) | 1997-12-22 | 2002-04-23 | Euro-Celtique, S.A. | Opioid agonist/opioid antagonist/acetaminophen combinations |
WO1999032119A1 (en) | 1997-12-22 | 1999-07-01 | Euro-Celtique, S.A. | Opioid agonist/antagonist combinations |
WO2000016776A1 (fr) * | 1998-09-18 | 2000-03-30 | Takeda Chemical Industries, Ltd. | Preparations a administrer par voie buccale a liberation lente |
US6806294B2 (en) | 1998-10-15 | 2004-10-19 | Euro-Celtique S.A. | Opioid analgesic |
DE19918325A1 (de) | 1999-04-22 | 2000-10-26 | Euro Celtique Sa | Verfahren zur Herstellung von Arzneiformen mit regulierter Wirkstofffreisetzung mittels Extrusion |
NZ529928A (en) | 1999-10-29 | 2005-10-28 | Euro Celtique Sa | Controlled release hydrocodone formulations |
US10179130B2 (en) | 1999-10-29 | 2019-01-15 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
HU229705B1 (en) | 2000-02-08 | 2014-05-28 | Euro Celtique Sa | Tamper-resistant oral opioid agonist formulations |
CA2400578C (en) | 2000-02-08 | 2007-01-02 | Euro-Celtique, S.A. | Controlled-release compositions containing opioid agonist and antagonist |
US6716449B2 (en) | 2000-02-08 | 2004-04-06 | Euro-Celtique S.A. | Controlled-release compositions containing opioid agonist and antagonist |
KR101045144B1 (ko) | 2000-10-30 | 2011-06-30 | 유로-셀티크 소시에떼 아노뉨 | 서방성 하이드로코돈 제형 |
UA81224C2 (uk) | 2001-05-02 | 2007-12-25 | Euro Celtic S A | Дозована форма оксикодону та її застосування |
US20110104214A1 (en) | 2004-04-15 | 2011-05-05 | Purdue Pharma L.P. | Once-a-day oxycodone formulations |
ATE493130T1 (de) | 2001-05-11 | 2011-01-15 | Endo Pharmaceuticals Inc | Opioid enthaltende arzneiform gegen missbrauch |
ATE376832T1 (de) * | 2001-07-06 | 2007-11-15 | Penwest Pharmaceuticals Co | Verzögert freisetzende formulierungen von oxymorphon |
CN1610551A (zh) | 2001-07-06 | 2005-04-27 | 恩德制药公司 | 用作止痛剂的6-羟基羟吗啡酮的肠胃外给药 |
US8329216B2 (en) * | 2001-07-06 | 2012-12-11 | Endo Pharmaceuticals Inc. | Oxymorphone controlled release formulations |
DE60230632D1 (de) | 2001-07-18 | 2009-02-12 | Euro Celtique Sa | Pharmazeutische kombinationen von oxycodon und naloxon |
US20030068375A1 (en) | 2001-08-06 | 2003-04-10 | Curtis Wright | Pharmaceutical formulation containing gelling agent |
US20030044458A1 (en) | 2001-08-06 | 2003-03-06 | Curtis Wright | Oral dosage form comprising a therapeutic agent and an adverse-effect agent |
ATE431738T1 (de) | 2001-08-06 | 2009-06-15 | Euro Celtique Sa | Opioid-agonist-formulierungen mit freisetzbarem und sequestriertem antagonist |
WO2003013433A2 (en) | 2001-08-06 | 2003-02-20 | Euro-Celtique S.A. | Sequestered antagonist formulations |
WO2003026743A2 (en) * | 2001-09-26 | 2003-04-03 | Penwest Pharmaceuticals Company | Opioid formulations having reduced potential for abuse |
EP2243471A1 (en) * | 2002-04-05 | 2010-10-27 | Euro-Celtique S.A. | Matrix for sustained, invariant and independent release of active compounds |
GB0209265D0 (en) | 2002-04-23 | 2002-06-05 | Novartis Ag | Organic compounds |
NZ536252A (en) * | 2002-04-29 | 2007-06-29 | Alza Corp | Methods and dosage forms for controlled delivery of oxycodone |
US20050106249A1 (en) * | 2002-04-29 | 2005-05-19 | Stephen Hwang | Once-a-day, oral, controlled-release, oxycodone dosage forms |
AU2003245345A1 (en) * | 2002-05-31 | 2003-12-19 | Alza Corporation | Dosage forms and compositions for osmotic delivery of variable dosages of oxycodone |
US20040001889A1 (en) | 2002-06-25 | 2004-01-01 | Guohua Chen | Short duration depot formulations |
US8557291B2 (en) * | 2002-07-05 | 2013-10-15 | Collegium Pharmaceutical, Inc. | Abuse-deterrent pharmaceutical compositions of opioids and other drugs |
US8840928B2 (en) * | 2002-07-05 | 2014-09-23 | Collegium Pharmaceutical, Inc. | Tamper-resistant pharmaceutical compositions of opioids and other drugs |
US10004729B2 (en) | 2002-07-05 | 2018-06-26 | Collegium Pharmaceutical, Inc. | Tamper-resistant pharmaceutical compositions of opioids and other drugs |
JP4694207B2 (ja) | 2002-07-05 | 2011-06-08 | コルジウム ファーマシューティカル, インコーポレイテッド | オピオイドおよび他の薬物に関する乱用抑止性の薬学的組成物 |
EP1545468A4 (en) * | 2002-09-20 | 2007-06-20 | Alpharma Inc | SUSTAINED RELEASE OPIOID PREPARATIONS AND METHODS OF USE |
DK1551372T3 (en) | 2002-09-20 | 2018-07-23 | Alpharma Pharmaceuticals Llc | SEQUERATION SUBSTANCES AND RELATED COMPOSITIONS AND PROCEDURES |
US20040110781A1 (en) * | 2002-12-05 | 2004-06-10 | Harmon Troy M. | Pharmaceutical compositions containing indistinguishable drug components |
DK1575569T3 (da) * | 2002-12-13 | 2011-01-10 | Durect Corp | Oralt indgivelsessystem omfattende flydende bærematerialer med høj viskositet |
US20040202717A1 (en) | 2003-04-08 | 2004-10-14 | Mehta Atul M. | Abuse-resistant oral dosage forms and method of use thereof |
TWI347201B (en) | 2003-04-21 | 2011-08-21 | Euro Celtique Sa | Pharmaceutical products,uses thereof and methods for preparing the same |
EP1479381A1 (en) * | 2003-05-19 | 2004-11-24 | Euro-Celtique S.A. | Pharmaceutical dosage form comprising a solid solution |
US20060165790A1 (en) * | 2003-06-27 | 2006-07-27 | Malcolm Walden | Multiparticulates |
TWI357815B (en) * | 2003-06-27 | 2012-02-11 | Euro Celtique Sa | Multiparticulates |
EP2298303A1 (en) | 2003-09-25 | 2011-03-23 | Euro-Celtique S.A. | Pharmaceutical combinations of hydrocodone and naltrexone |
US20050074493A1 (en) * | 2003-10-03 | 2005-04-07 | Mehta Atul M. | Extended release formulations of opioids and method of use thereof |
CA2548917C (en) | 2003-12-11 | 2014-09-23 | Sepracor Inc. | Combination of a sedative and a neurotransmitter modulator, and methods for improving sleep quality and treating depression |
WO2006079550A2 (en) * | 2005-01-28 | 2006-08-03 | Euro-Celtique S.A. | Alcohol resistant dosage forms |
TWI365880B (en) | 2004-03-30 | 2012-06-11 | Euro Celtique Sa | Process for preparing oxycodone hydrochloride having less than 25 ppm 14-hydroxycodeinone and oxycodone hydrochloride composition,pharmaceutical dosage form,sustained release oeal dosage form and pharmaceutically acceptable package having less than 25 pp |
KR101053558B1 (ko) * | 2004-03-30 | 2011-08-03 | 유로-셀띠끄 소시에떼 아노님 | 흡착제 및 억제제를 포함하는 내변조성 제형 |
US20050226929A1 (en) * | 2004-04-12 | 2005-10-13 | Jianbo Xie | Controlled release opioid analgesic formulation |
US20050266082A1 (en) * | 2004-05-26 | 2005-12-01 | Patel Satishkumar A | Preparation of stable paroxetine HC1 ER tablets using a melt granulation process |
EP1604666A1 (en) | 2004-06-08 | 2005-12-14 | Euro-Celtique S.A. | Opioids for the treatment of the Chronic Obstructive Pulmonary Disease (COPD) |
EP1604667A1 (en) | 2004-06-08 | 2005-12-14 | Euro-Celtique S.A. | Opioids for the treatment of the restless leg syndrome |
ES2653568T3 (es) | 2004-06-12 | 2018-02-07 | Collegium Pharmaceutical, Inc. | Formulaciones de fármacos para la prevención del abuso |
US9308164B2 (en) * | 2004-06-30 | 2016-04-12 | Sovereign Pharmaceuticals, Llc | Hyoscyamine dosage form |
GB2418854B (en) | 2004-08-31 | 2009-12-23 | Euro Celtique Sa | Multiparticulates |
EA014852B1 (ru) | 2004-09-17 | 2011-02-28 | Дьюрект Корпорейшн | Система контролируемой доставки |
TWI369203B (en) | 2004-11-22 | 2012-08-01 | Euro Celtique Sa | Methods for purifying trans-(-)-△9-tetrahydrocannabinol and trans-(+)-△9-tetrahydrocannabinol |
EP1702558A1 (en) | 2005-02-28 | 2006-09-20 | Euro-Celtique S.A. | Method and device for the assessment of bowel function |
EP1695700A1 (en) * | 2005-02-28 | 2006-08-30 | Euro-Celtique S.A. | Dosage form containing oxycodone and naloxone |
US20090214640A1 (en) * | 2005-03-04 | 2009-08-27 | Intelgenx Cporp. | Delayed release pharmaceutical oral dosage form and method of making same |
MY148074A (en) * | 2005-05-10 | 2013-02-28 | Novartis Ag | Pharmaceutical compositions comprising imatinib and a release retardant |
DK1888080T3 (da) * | 2005-06-09 | 2010-07-19 | Euro Celtique Sa | Farmaceutiske sammensætninger af en neuroaktiv steroid og anvendelser deraf |
TWI366460B (en) * | 2005-06-16 | 2012-06-21 | Euro Celtique Sa | Cannabinoid active pharmaceutical ingredient for improved dosage forms |
JP5095615B2 (ja) | 2005-06-27 | 2012-12-12 | バリアント・インターナショナル・(バルバドス)・ソサイアティーズ・ウィズ・リストリクティッド・ライアビリティ | ブプロピオン塩の放出調整製剤 |
US20070027105A1 (en) | 2005-07-26 | 2007-02-01 | Alza Corporation | Peroxide removal from drug delivery vehicle |
EP1813276A1 (en) * | 2006-01-27 | 2007-08-01 | Euro-Celtique S.A. | Tamper resistant dosage forms |
US20070190141A1 (en) * | 2006-02-16 | 2007-08-16 | Aaron Dely | Extended release opiate composition |
US20070212414A1 (en) * | 2006-03-08 | 2007-09-13 | Penwest Pharmaceuticals Co. | Ethanol-resistant sustained release formulations |
US20070281017A1 (en) * | 2006-06-06 | 2007-12-06 | Endo Pharmaceuticals Inc., A Delaware Corporation | Sustained release oxycodone composition with acrylic polymer and metal hydroxide |
US20070281016A1 (en) * | 2006-06-06 | 2007-12-06 | Endo Pharmaceuticals Inc., A Delaware Corporation | Sustained release oxycodone composition with acrylic polymer and surfactant |
US20080069891A1 (en) | 2006-09-15 | 2008-03-20 | Cima Labs, Inc. | Abuse resistant drug formulation |
CN101677963B (zh) | 2006-06-19 | 2012-05-30 | 奥尔制药公司 | 药物组合物 |
US20080075771A1 (en) * | 2006-07-21 | 2008-03-27 | Vaughn Jason M | Hydrophilic opioid abuse deterrent delivery system using opioid antagonists |
BRPI0714484A2 (pt) * | 2006-08-16 | 2013-04-24 | Auspex Pharmaceuticals Inc | composto, mÉtodo de tratar um mamÍfero sofrendo de uma doenÇa ou condiÇço, mÉtodo de tratar um memÍfero sofrendo de uma doenÇa, desordem, sintoma ou condiÇço e composiÇço farmacÊutica |
SA07280459B1 (ar) | 2006-08-25 | 2011-07-20 | بيورديو فارما إل. بي. | أشكال جرعة صيدلانية للتناول عن طريق الفم مقاومة للعبث تشتمل على مسكن شبه أفيوني |
US8445018B2 (en) | 2006-09-15 | 2013-05-21 | Cima Labs Inc. | Abuse resistant drug formulation |
PT2117521E (pt) | 2006-11-03 | 2012-09-10 | Durect Corp | Sistemas de administração transdérmica que compreendem bupivacaína |
US20080220064A1 (en) * | 2006-12-06 | 2008-09-11 | Ramesh Ketkar Anant | Extended release matrix formulations of morphine |
GB0624880D0 (en) * | 2006-12-14 | 2007-01-24 | Johnson Matthey Plc | Improved method for making analgesics |
US8202542B1 (en) | 2007-05-31 | 2012-06-19 | Tris Pharma | Abuse resistant opioid drug-ion exchange resin complexes having hybrid coatings |
US20090124650A1 (en) * | 2007-06-21 | 2009-05-14 | Endo Pharmaceuticals, Inc. | Method of Treating Pain Utilizing Controlled Release Oxymorphone Pharmaceutical Compositions and Instructions on Effects of Alcohol |
AU2008347158B8 (en) | 2007-12-06 | 2013-08-22 | Durect Corporation | Oral pharmaceutical dosage forms |
US8623418B2 (en) | 2007-12-17 | 2014-01-07 | Alpharma Pharmaceuticals Llc | Pharmaceutical composition |
US20090246276A1 (en) | 2008-01-28 | 2009-10-01 | Graham Jackson | Pharmaceutical Compositions |
US20100003322A1 (en) * | 2008-07-03 | 2010-01-07 | Lai Felix S | Enteric coated hydrophobic matrix formulation |
US20100260844A1 (en) | 2008-11-03 | 2010-10-14 | Scicinski Jan J | Oral pharmaceutical dosage forms |
DK2405915T3 (en) | 2009-03-10 | 2019-02-11 | Euro Celtique Sa | PHARMACEUTICAL COMPOSITIONS WITH IMMEDIATE RELEASE INCLUDING OXYCODON AND NALOXON |
FR2946533A1 (fr) | 2009-06-12 | 2010-12-17 | Ethypharm Sa | Reduction des fluctuations plasmatiques d'opioides. |
US10668060B2 (en) | 2009-12-10 | 2020-06-02 | Collegium Pharmaceutical, Inc. | Tamper-resistant pharmaceutical compositions of opioids and other drugs |
EP2568977A1 (en) | 2010-05-11 | 2013-03-20 | Cima Labs Inc. | Alcohol-resistant metoprolol-containing extended- release oral dosage forms |
CN103370058A (zh) | 2010-12-22 | 2013-10-23 | 普渡制药公司 | 包覆的抗篡改控制释放剂型 |
CN107412173A (zh) | 2010-12-23 | 2017-12-01 | 普渡制药公司 | 抗篡改固体口服剂型 |
US20130143867A1 (en) | 2011-12-02 | 2013-06-06 | Sychroneuron Inc. | Acamprosate formulations, methods of using the same, and combinations comprising the same |
CA3120681A1 (en) | 2012-04-17 | 2013-10-24 | Purdue Pharma L.P. | Systems and methods for treating an opioid-induced adverse pharmacodynamic response |
JP6236447B2 (ja) | 2012-07-16 | 2017-11-22 | ローズ テクノロジーズ | 改善されたオピオイド合成方法 |
CN104507947B (zh) | 2012-07-16 | 2017-06-27 | 罗德科技公司 | 用于改进的阿片样物质合成的方法 |
MX2015010041A (es) | 2013-02-05 | 2015-10-30 | Purdue Pharma Lp | Formulacion farmaceuticas resistentes a la alteracion. |
CN105120659A (zh) | 2013-03-15 | 2015-12-02 | 度瑞公司 | 用于降低溶解可变性的具有流变改性剂的组合物 |
US10751287B2 (en) | 2013-03-15 | 2020-08-25 | Purdue Pharma L.P. | Tamper resistant pharmaceutical formulations |
WO2014197744A1 (en) | 2013-06-05 | 2014-12-11 | Synchroneuron, Inc. | Acamprosate formulations, methods of using the same, and combinations comprising the same |
KR20180037074A (ko) | 2013-07-23 | 2018-04-10 | 유로-셀티큐 에스.에이. | 장내 세균총이상을 초래하고/하거나 장내 박테리아 전위에 대한 위험을 증가시키는 질환과 통증으로 인해 고통받고 있는 환자에서 통증을 치료하는데 사용하기 위한 옥시코돈과 날록손의 조합물 |
EP3027622B8 (en) | 2013-08-02 | 2019-06-12 | Johnson Matthey Public Limited Company | Process for the preparation of oxymorphone |
WO2015107472A1 (en) | 2014-01-15 | 2015-07-23 | Rhodes Technologies | Process for improved oxymorphone synthesis |
JP2017502991A (ja) | 2014-01-15 | 2017-01-26 | ローズ テクノロジーズ | 改良されたオキシコドン合成のための方法 |
US9062063B1 (en) | 2014-03-21 | 2015-06-23 | Johnson Matthey Public Limited Company | Forms of oxymorphone hydrochloride |
US9849124B2 (en) | 2014-10-17 | 2017-12-26 | Purdue Pharma L.P. | Systems and methods for treating an opioid-induced adverse pharmacodynamic response |
US9918979B2 (en) | 2015-01-29 | 2018-03-20 | Johnson Matthey Public Limited Company | Process of preparing low ABUK oxymorphone hydrochloride |
US9943513B1 (en) | 2015-10-07 | 2018-04-17 | Banner Life Sciences Llc | Opioid abuse deterrent dosage forms |
US20180303757A1 (en) | 2015-10-23 | 2018-10-25 | Kashiv Pharma Llc | Enhanced abuse-deterrent formulations of oxycodone |
US10335405B1 (en) | 2016-05-04 | 2019-07-02 | Patheon Softgels, Inc. | Non-burst releasing pharmaceutical composition |
US9737530B1 (en) | 2016-06-23 | 2017-08-22 | Collegium Pharmaceutical, Inc. | Process of making stable abuse-deterrent oral formulations |
US10335375B2 (en) | 2017-05-30 | 2019-07-02 | Patheon Softgels, Inc. | Anti-overingestion abuse deterrent compositions |
WO2019087084A1 (en) | 2017-11-02 | 2019-05-09 | Eman Biodiscoveries Sd. Bhd. | Extract of orthosiphon stamineus, formulations, and uses thereof |
CN115666621A (zh) | 2020-01-13 | 2023-01-31 | 度勒科特公司 | 具有减少的杂质的持续释放药物递送系统及相关方法 |
KR20230000634U (ko) | 2021-09-16 | 2023-03-23 | 장상환 | 분리가능한 쇠스랑 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2805977A (en) * | 1955-01-04 | 1957-09-10 | Smith Kline French Lab | Sustained release pharmaceutical preparation |
GB1405088A (en) * | 1971-06-03 | 1975-09-03 | Mundipharma Ag | Slow release formulation |
US3965256A (en) * | 1972-05-16 | 1976-06-22 | Synergistics | Slow release pharmaceutical compositions |
SE418247B (sv) * | 1975-11-17 | 1981-05-18 | Haessle Ab | Sett att framstella kroppar med reglerad frigoring av en aktiv komponent |
SE7813246L (sv) * | 1978-12-22 | 1980-06-23 | Haessle Ab | Fast farmaceutisk beredning innehallande kroppar med flera ytskikt |
SE8003805L (sv) * | 1980-05-21 | 1981-11-22 | Haessle Ab | En farmaceutisk beredning med forbettrade utlosningsegenskap |
ATE14379T1 (de) * | 1981-04-27 | 1985-08-15 | Haessle Ab | Pharmazeutisches praeparat. |
DE3124983A1 (de) * | 1981-06-25 | 1983-01-20 | Meditest Inst Fuer Medizinisch | Arzneiformen zur oralen verabreichung |
US4443428A (en) * | 1982-06-21 | 1984-04-17 | Euroceltique, S.A. | Extended action controlled release compositions |
DK58983D0 (da) * | 1983-02-11 | 1983-02-11 | Leo Pharm Prod Ltd | Farmaceutisk praeparat |
JPS6143108A (ja) * | 1984-08-03 | 1986-03-01 | Nippon Shinyaku Co Ltd | 医薬品製剤及びその製造法 |
NL8500724A (nl) * | 1985-03-13 | 1986-10-01 | Univ Groningen | Inrichtingen voor geregelde afgifte van werkzame stoffen, alsmede werkwijze ter vervaardiging daarvan. |
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1986
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- 1987-07-18 DZ DZ870126A patent/DZ1112A1/fr active
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